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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 821813, 10 pages
http://dx.doi.org/10.1155/2013/821813
Research Article

Andrographolide, a Novel NF-κB Inhibitor, Induces Vascular Smooth Muscle Cell Apoptosis via a Ceramide-p47phox-ROS Signaling Cascade

1Graduate Institute of Medical Sciences, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan
2Department of Pharmacology, School of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan
3Department of Microbiology and Immunology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan

Received 30 October 2013; Accepted 4 December 2013

Academic Editor: Mao-Hsiung Yen

Copyright © 2013 Yu-Ying Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Atherosclerosis is linked with the development of many cardiovascular complications. Abnormal proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in the development of atherosclerosis. Accordingly, the apoptosis of VSMCs, which occurs in the progression of vascular proliferation, may provide a beneficial strategy for managing cardiovascular diseases. Andrographolide, a novel nuclear factor-κB inhibitor, is the most active and critical constituent isolated from the leaves of Andrographis paniculata. Recent studies have indicated that andrographolide is a potential therapeutic agent for treating cancer through the induction of apoptosis. In this study, the apoptosis-inducing activity and mechanisms in andrographolide-treated rat VSMCs were characterized. Andrographolide significantly induced reactive oxygen species (ROS) formation, p53 activation, Bax, and active caspase-3 expression, and these phenomena were suppressed by pretreating the cells with N-acetyl-L-cysteine, a ROS scavenger, or diphenylene iodonium, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) inhibitor. Furthermore, p47phox, a Nox subunit protein, was phosphorylated in andrographolide-treated rat VSMCs. However, pretreatment with 3-O-methyl-sphingomyelin, a neutral sphingomyelinase inhibitor, significantly inhibited andrographolide-induced p47phox phosphorylation as well as Bax and active caspase-3 expression. Our results collectively demonstrate that andrographolide-reduced cell viability can be attributed to apoptosis in VSMCs, and this apoptosis-inducing activity was associated with the ceramide-p47phox-ROS signaling cascade.